The average life-expectancy of end-stage renal disease patients starting maintenance dialysis in the US is about three years. Most clinical trials that tested a variety of potentially promising interventions have been unable to demonstrate a reduction in death risk of dialysis patients. The continued quest to improve outcomes has led to modifications of the conventional hemodialysis prescription to either significantly increase treatment time for each session or the frequency of therapy. The benefits on the co-primary composite of death risk or left ventricular mass increase seen in the recently concluded Frequent Hemodialysis Network (FHN) Daily Trial lends support to these modified prescriptions. However, the therapies being increasingly used in clinical practice differ from the interventions tested in the FHN trial. Nocturnal in-center hemodialysis (NICHD) provides longer treatment times but is generally delivered at a lower frequency (thrice weekly) than nocturnal home hemodialysis (5-6 times/ week) studied by FHN. Similarly, the most popular form of daily hemodialysis is performed at home with a device that is user-friendly but delivers lower solute clearances (short-daily, low-flow, home hemodialysis, SD-LF-HHD) than systems used in the FHN Daily Trial. NICHD or SD-LF-HHD patients cannot be identified in any publicly available data-source, including from the United States Renal Data System (USRDS) but this information is readily available in data from dialysis providers. In this project, we will obtain, refine, and ink data from DaVita, an organization that treats almost one-third of all US dialysis patients across 43 states, with the USRDS to examine outcomes of NICHD and SD-LF-HHD patients (n=2400, and 3500 respectively). The comparisons of these therapies with peritoneal dialysis and/or thrice-weekly conventional hemodialysis will be adequately powered for all-cause mortality, the primary outcome measure. The novel analytic strategy will use marginal structural models, a non-parametric causal model and will adjust for confounding from (1) baseline patient characteristics, (2) time-varying modality change, and (3) censoring for transplantation or drop-out. Confounding from site of care (TWICHD outcomes in facilities with/without NICHD programs) will be examined and to account for difficult-to-measure bias from patients who choose self-care home dialysis SD-LF-HHD outcomes will compared to PD, another home dialysis therapy. The high granularity of the linked data will allow us to study the association of NICHD and SD-LF-HHD with additional outcomes including cause-specific mortality, hospitalizations, solute clearances, hypertension, anemia, mineral metabolism, nutrition, dialysis tolerability, and vascular access morbidity. The DaVita-USRDS data linkage will provide access to Medicare claims data which will be used to calculate incremental societal cost-effectiveness or cost-savings with NICHD and SD-LF-HHD. Thus, this 3-year proposal will efficiently generate a wealth of time-sensitive information about two increasingly popular dialysis therapies that will be of immediate clinical and public health relevance and inform decision making by physicians, patients, providers, and payers. PUBLIC HEALTH RELEVANCE: The average life expectancy of patients with end-stage kidney disease starting maintenance dialysis in the United States is about three years and these patients spend 13 days in the hospital every year. Many more patients are being treated with hemodialysis therapy with either longer treatment times, or performed more frequently than thrice weekly. The overarching goal of this proposal is to determine whether these modifications to conventional hemodialysis treatments lead to improvements in life-expectancy, or reduction in hospitalizations for dialysis patients, and generate cost-savings for the healthcare system.